Synthesis, biological evaluation, molecular docking and in silico ADME studies of phenacyl esters of N-Phthaloyl amino acids as pancreatic lipase inhibitors

Abstract

In continuation of our previous study, a series of phenacyl esters of N-phthaloyl amino acids were synthesized and screened for their in vitro pancreatic lipase inhibitory activity. N-phthloylation of amino acids and subsequent esterification with different phenacyl bromides in presence of N,N-Dimethylformamide (DMF) afforded the corresponding phenacyl esters in quantitative yields. The synthesized compounds were found to have potent in vitro pancreatic lipase inhibitory activity in 0.9–2.5 μM range. The most active compound 2‐(4‐bromophenyl)‐2‐oxoethyl 3‐(1,3‐dioxo‐2,3‐ dihydro‐1H‐isoindol‐2‐yl) propanoate (4g) displayed very good pancreatic lipase inhibitory activity with the IC50 value 0.9 μM. To understand the enzyme inhibition and to ensure the lead likeness, in silico docking and ADME studies were carried on title compounds. The in vitro pancreatic lipase inhibitory activities and in silico studies suggested that this N-phthaloyl phenacyl ester analogues could be a potential lead and may be taken to the next level of antiobesity drug development.